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This project will investigate the development of large-scale neural networks in infancy. We will collect longitudinal data from infants at 8, 12, 18, and 24 months of age using functional near-infrared spectroscopy (fNIRS). Infants will engage in two tasks so that we can measure brain activity at rest (i.e., resting-state functional connectivity) and when infants are actively engaged in learning (i.e., task-based functional connectivity).

The central aim of this study is to investigate the relationship between neural reward sensitivity and cognitive control across adolescent development. To examine this relationship, we plan to use the longitudinal fMRI imaging and behavioral data provided by the Adolescent Brain Cognitive Development Study database. The analyses described here are designed to test the following questions: 1) Does neural reward sensitivity predict cognitive control during development from 9 to 14 years old? 2) Does the development of neural reward sensitivity predict cortical-subcortical functional connectivity supporting cognitive control? 3) Does cognitive control-related cortical-subcortical connectivity mediate the relationship between neural reward sensitivity and cognitive control? These findings will deepen our understanding of the adaptive significance of reward sensitivity and help differentiate between neural models explaining adolescent behavior.

Face processing has been shown to have a fundamental role to learn social skills and attend to social information (Rajhans et al., 2016). Facial emotion processing is critical to social cognitive ability, and previous research has suggested that language plays a role in the development of social cognitive skills, including non-verbal emotion recognition tasks. Bigelow et al. (2022) showed that several ERP components were correlated with language development during childhood, and that it depends on facial expression. They found that P100 latency for negative expressions increased with language, while Late Positive Potential (LPP) amplitude increased with language for negative and neutral expressions. Several Event-related Potential (ERP) components have shown to reflect these abilities. ERPs are defined as very small voltages generated in the brain structures in response to specific events or stimuli. Furthermore, N290 has been shown to reflect facial emotion processing in young children, with smaller amplitude in response to fearful expressions, compared to happy or neutral ones. Additionally, N290 amplitudes are reduced in young compared to older children; this is thought to be due to the high-level cognition that has been developed across time (van den Boomen; Xie et al., 2019). However, controversial findings for N290 amplitudes and latencies have been found. For instance, Rajhans et al. (2016) showed that no effects were observed for face-sensitive processing as reflected in the N290, thought to be involved in face encoding in infants. Therefore, the current study will provide insights about the neural correlates of infant facial emotion processing in the second year of life and will have the potential to serve as a reference on the typical development of the neural mechanisms underlying infant facial emotion processing. Therefore, using baseline visit data from the Kia Tīmata Pai (KTP) study, we aim to conduct cross-sectional analysis to investigate how N290 amplitude and latency 1) associate with age in early development 2) differ in response to different emotional stimuli (angry, fearful, happy faces). We will assess a total of 200 children, between 13 and 30 months old. EEG data were collected while infants were viewing images of angry, happy, and neutral faces. Furthermore, we will 3) investigate the relationship between N290 amplitudes and latencies, and oral language development. We expect to see greater amplitude and later latency to be associated with better performance in the oral language measures. The novelty of this study is the combination of EEG and oral language measures. Not many studies investigated the associations between these two variables across early development.

Face processing has been shown to have a fundamental role to learn social skills and attend to social information (Rajhans et al., 2016). Facial emotion processing is critical to social cognitive ability, and previous research has suggested that language plays a role in the development of social cognitive skills, including non-verbal emotion recognition tasks. Bigelow et al. (2022) showed that several ERP components were correlated with language development during childhood, and that it depends on facial expression. They found that P100 latency for negative expressions increased with language, while Late Positive Potential (LPP) amplitude increased with language for negative and neutral expressions. Several Event-related Potential (ERP) components have shown to reflect these abilities. ERPs are defined as very small voltages generated in the brain structures in response to specific events or stimuli. Furthermore, N290 has been shown to reflect facial emotion processing in young children, with smaller amplitude in response to fearful expressions, compared to happy or neutral ones. Additionally, N290 amplitudes are reduced in young compared to older children; this is thought to be due to the high-level cognition that has been developed across time (van den Boomen; Xie et al., 2019). However, controversial findings for N290 amplitudes and latencies have been found. For instance, Rajhans et al. (2016) showed that no effects were observed for face-sensitive processing as reflected in the N290, thought to be involved in face encoding in infants. Therefore, the current study will provide insights about the neural correlates of infant facial emotion processing in the second year of life and will have the potential to serve as a reference on the typical development of the neural mechanisms underlying infant facial emotion processing. Therefore, using baseline visit data from the Kia Tīmata Pai (KTP) study, we aim to conduct cross-sectional analysis to investigate how N290 amplitude and latency 1) associate with age in early development 2) differ in response to different emotional stimuli (angry, fearful, happy faces). We will assess a total of 200 children, between 13 and 30 months old. EEG data were collected while infants were viewing images of angry, happy, and neutral faces. Furthermore, we will 3) investigate the relationship between N290 amplitudes and latencies, and oral language development. We expect to see greater amplitude and later latency to be associated with better performance in the oral language measures. The novelty of this study is the combination of EEG and oral language measures. Not many studies investigated the associations between these two variables across early development.

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This article is from Human Molecular Genetics , volume 23 . Abstract Urofacial syndrome (UFS; previously Ochoa syndrome) is an autosomal recessive disease characterized by incomplete bladder emptying during micturition. This is associated with a dyssynergia in which the urethral walls contract at the same time as the detrusor smooth muscle in the body of the bladder. UFS is also characterized by an abnormal facial expression upon smiling, and bilateral weakness in the distribution of the facial nerve has been reported. Biallelic mutations in HPSE2 occur in UFS. This gene encodes heparanase 2, a protein which inhibits the activity of heparanase. Here, we demonstrate, for the first time, an in vivo developmental role for heparanase 2. We identified the Xenopus orthologue of heparanase 2 and showed that the protein is localized to the embryonic ventrolateral neural tube where motor neurons arise. Morpholino-induced loss of heparanase 2 caused embryonic skeletal muscle paralysis, and morphant motor neurons had aberrant morphology including less linear paths and less compactly-bundled axons than normal. Biochemical analyses demonstrated that loss of heparanase 2 led to upregulation of fibroblast growth factor 2/phosphorylated extracellular signal-related kinase signalling and to alterations in levels of transcripts encoding neural- and muscle-associated molecules. Thus, a key role of heparanase 2 is to buffer growth factor signalling in motor neuron development. These results shed light on the pathogenic mechanisms underpinning the clinical features of UFS and support the contention that congenital peripheral neuropathy is a key feature of this disorder.

This article is from EvoDevo , volume 4 . Abstract Background: Arthropod and vertebrate appendages appear to have evolved via parallel co-option of a plesiomorphic gene regulatory network. Our previous work implies that annelids evolved unrelated appendage-forming mechanisms; we therefore found no support for homology of parapodia and arthropodia at the level of the whole appendage. We expand on that study here by asking whether expression of the LIM homeobox (Lhx) genes apterous and lim1 in the annelid Neanthes arenaceodentata supports homology of the dorsal branches as well as the proximodistal axes of parapodia and arthropodia. In addition, we explore whether the neural expression of apterous and lim1 in Neanthes supports the putative ancestral function of the Lhx gene family in regulating the differentiation and maintenance of neuronal subtypes. Results: Both genes exhibit continuous expression in specific portions of the developing central nervous system, from hatching to at least the 13-chaetiger stage. For example, nerve cord expression occurs in segmentally iterated patterns consisting of diffuse sets of many lim1-positive cells and comparatively fewer, clustered pairs of apterous-positive cells. Additionally, continuous apterous expression is observed in presumed neurosecretory ganglia of the posterior brain, while lim1 is continuously expressed in stomatogastric ganglia of the anterior brain. apterous is also expressed in the jaw sacs, dorsal parapodial muscles, and a presumed pair of cephalic sensory organs, whereas lim1 is expressed in multiple pharyngeal ganglia, the segmental peripheral nervous system, neuropodial chaetal sac muscles, and parapodial ligules. Conclusions: The early and persistent nervous system expression of apterous and lim1 in Neanthes juveniles supports conservation of Lhx function in bilaterian neural differentiation and maintenance. Our results also suggest that diversification of parapodial muscle precursors involves a complementary LIM code similar to those generating distinct neuronal identities in fly and mouse nerve cords. Expression of apterous and lim1 in discrete components of developing parapodia is intriguing but does not map to comparable expression of these genes in developing arthropod appendages. Thus, annelid and arthropod appendage development apparently evolved, in part, via distinct co-option of the neuronal regulatory architecture. These divergent patterns of apterous and lim1 activity seemingly reflect de novo origins of parapodia and arthropodia, although we discuss alternative hypotheses.

This article is from EvoDevo , volume 4 . Abstract Background: Arthropod and vertebrate appendages appear to have evolved via parallel co-option of a plesiomorphic gene regulatory network. Our previous work implies that annelids evolved unrelated appendage-forming mechanisms; we therefore found no support for homology of parapodia and arthropodia at the level of the whole appendage. We expand on that study here by asking whether expression of the LIM homeobox (Lhx) genes apterous and lim1 in the annelid Neanthes arenaceodentata supports homology of the dorsal branches as well as the proximodistal axes of parapodia and arthropodia. In addition, we explore whether the neural expression of apterous and lim1 in Neanthes supports the putative ancestral function of the Lhx gene family in regulating the differentiation and maintenance of neuronal subtypes. Results: Both genes exhibit continuous expression in specific portions of the developing central nervous system, from hatching to at least the 13-chaetiger stage. For example, nerve cord expression occurs in segmentally iterated patterns consisting of diffuse sets of many lim1-positive cells and comparatively fewer, clustered pairs of apterous-positive cells. Additionally, continuous apterous expression is observed in presumed neurosecretory ganglia of the posterior brain, while lim1 is continuously expressed in stomatogastric ganglia of the anterior brain. apterous is also expressed in the jaw sacs, dorsal parapodial muscles, and a presumed pair of cephalic sensory organs, whereas lim1 is expressed in multiple pharyngeal ganglia, the segmental peripheral nervous system, neuropodial chaetal sac muscles, and parapodial ligules. Conclusions: The early and persistent nervous system expression of apterous and lim1 in Neanthes juveniles supports conservation of Lhx function in bilaterian neural differentiation and maintenance. Our results also suggest that diversification of parapodial muscle precursors involves a complementary LIM code similar to those generating distinct neuronal identities in fly and mouse nerve cords. Expression of apterous and lim1 in discrete components of developing parapodia is intriguing but does not map to comparable expression of these genes in developing arthropod appendages. Thus, annelid and arthropod appendage development apparently evolved, in part, via distinct co-option of the neuronal regulatory architecture. These divergent patterns of apterous and lim1 activity seemingly reflect de novo origins of parapodia and arthropodia, although we discuss alternative hypotheses.

This article is from EvoDevo , volume 4 . Abstract Background: Arthropod and vertebrate appendages appear to have evolved via parallel co-option of a plesiomorphic gene regulatory network. Our previous work implies that annelids evolved unrelated appendage-forming mechanisms; we therefore found no support for homology of parapodia and arthropodia at the level of the whole appendage. We expand on that study here by asking whether expression of the LIM homeobox (Lhx) genes apterous and lim1 in the annelid Neanthes arenaceodentata supports homology of the dorsal branches as well as the proximodistal axes of parapodia and arthropodia. In addition, we explore whether the neural expression of apterous and lim1 in Neanthes supports the putative ancestral function of the Lhx gene family in regulating the differentiation and maintenance of neuronal subtypes. Results: Both genes exhibit continuous expression in specific portions of the developing central nervous system, from hatching to at least the 13-chaetiger stage. For example, nerve cord expression occurs in segmentally iterated patterns consisting of diffuse sets of many lim1-positive cells and comparatively fewer, clustered pairs of apterous-positive cells. Additionally, continuous apterous expression is observed in presumed neurosecretory ganglia of the posterior brain, while lim1 is continuously expressed in stomatogastric ganglia of the anterior brain. apterous is also expressed in the jaw sacs, dorsal parapodial muscles, and a presumed pair of cephalic sensory organs, whereas lim1 is expressed in multiple pharyngeal ganglia, the segmental peripheral nervous system, neuropodial chaetal sac muscles, and parapodial ligules. Conclusions: The early and persistent nervous system expression of apterous and lim1 in Neanthes juveniles supports conservation of Lhx function in bilaterian neural differentiation and maintenance. Our results also suggest that diversification of parapodial muscle precursors involves a complementary LIM code similar to those generating distinct neuronal identities in fly and mouse nerve cords. Expression of apterous and lim1 in discrete components of developing parapodia is intriguing but does not map to comparable expression of these genes in developing arthropod appendages. Thus, annelid and arthropod appendage development apparently evolved, in part, via distinct co-option of the neuronal regulatory architecture. These divergent patterns of apterous and lim1 activity seemingly reflect de novo origins of parapodia and arthropodia, although we discuss alternative hypotheses.

This article is from Acta Neuropathologica Communications , volume 2 . Abstract Background: Axon degeneration is a characteristic feature of multiple neuropathologic states and is also a mechanism of physiological neurodevelopmental pruning. The vast majority of in vivo studies looking at axon degeneration have relied on the use of classical silver degeneration stains, which have many limitations including lack of molecular specificity and incompatibility with immunolabeling methods. Because Wallerian degeneration is well known to involve cytoskeletal disassembly and because caspases are recently implicated in aspects of this process, we asked whether antibodies directed at caspase-generated neoepitopes of beta-actin and alpha-tubulin would be useful immunohistochemical markers of pathological and developmental axon degeneration. Results: Here we demonstrate that several forms of axon degeneration involve caspase-mediated cleavage of these cytoskeletal elements and are well-visualized using this approach. We demonstrate the generation of caspase-induced neoepitopes in a) an in vitro neuronal culture model using nerve growth factor-deprivation-induced degeneration and b) an in vivo model using ethanol-induced neuronal apoptosis, and c) during normal developmental pruning and physiological turnover of neurons. Conclusions: Our findings support recent experimental data that suggests caspase-3 and caspase-6 have specific non-redundant roles in developmental pruning. Finally, these findings may have clinical utility, as these markers highlight degenerating neurites in human hypoxic-ischemic injury. Our work not only confirms a common downstream mechanism involved in axon degeneration, but also illuminates the potential utility of caspase-cleavage-neoepitope antibodies as markers of neurodegeneration.

This article is from PLoS ONE , volume 9 . Abstract Heparan sulfate proteoglycans (HSPGs) play critical roles in the development and adult physiology of all metazoan organisms. Most of the known molecular interactions of HSPGs are attributed to the structurally highly complex heparan sulfate (HS) glycans. However, whether a specific HSPG (such as syndecan) contains HS modifications that differ from another HSPG (such as glypican) has remained largely unresolved. Here, a neural model in C. elegans is used to demonstrate for the first time the relationship between specific HSPGs and HS modifications in a defined biological process in vivo. HSPGs are critical for the migration of hermaphrodite specific neurons (HSNs) as genetic elimination of multiple HSPGs leads to 80% defect of HSN migration. The effects of genetic elimination of HSPGs are additive, suggesting that multiple HSPGs, present in the migrating neuron and in the matrix, act in parallel to support neuron migration. Genetic analyses suggest that syndecan/sdn-1 and HS 6-O-sulfotransferase, hst-6, function in a linear signaling pathway and glypican/lon-2 and HS 2-O-sulfotransferase, hst-2, function together in a pathway that is parallel to sdn-1 and hst-6. These results suggest core protein specific HS modifications that are critical for HSN migration. In C. elegans, the core protein specificity of distinct HS modifications may be in part regulated at the level of tissue specific expression of genes encoding for HSPGs and HS modifying enzymes. Genetic analysis reveals that there is a delicate balance of HS modifications and eliminating one HS modifying enzyme in a compromised genetic background leads to significant changes in the overall phenotype. These findings are of importance with the view of HS as a critical regulator of cell signaling in normal development and disease.

This article is from Redox Biology , volume 2 . Abstract Glutaredoxin 2 is a vertebrate specific oxidoreductase of the thioredoxin family of proteins modulating the intracellular thiol pool. Thereby, glutaredoxin 2 is important for specific redox signaling and regulates embryonic development of brain and vasculature via reversible oxidative posttranslational thiol modifications. Here, we describe that glutaredoxin 2 is also required for successful heart formation. Knock-down of glutaredoxin 2 in zebrafish embryos inhibits the invasion of cardiac neural crest cells into the primary heart field. This leads to impaired heart looping and subsequent obstructed blood flow. Glutaredoxin 2 specificity of the observed phenotype was confirmed by rescue experiments. Active site variants of glutaredoxin 2 revealed that the (de)-glutathionylation activity is required for proper heart formation. Our data suggest that actin might be one target during glutaredoxin 2 regulated cardiac neural crest cell migration and embryonic heart development. In summary, this work represents further evidence for the general importance of redox signaling in embryonic development and highlights additionally the importance of glutaredoxin 2 during embryogenesis.

This article is from Genome Research , volume 23 . Abstract The neural crest is an excellent model system for the study of cell type diversification during embryonic development due to its multipotency, motility, and ability to form a broad array of derivatives ranging from neurons and glia, to cartilage, bone, and melanocytes. As a uniquely vertebrate cell population, it also offers important clues regarding vertebrate origins. In the past 30 yr, introduction of recombinant DNA technology has facilitated the dissection of the genetic program controlling neural crest development and has provided important insights into gene regulatory mechanisms underlying cell migration and differentiation. More recently, new genomic approaches have provided a platform and tools that are changing the depth and breadth of our understanding of neural crest development at a “systems” level. Such advances provide an insightful view of the regulatory landscape of neural crest cells and offer a new perspective on developmental as well as stem cell and cancer biology.

This article is from Genome Research , volume 23 . Abstract The neural crest is an excellent model system for the study of cell type diversification during embryonic development due to its multipotency, motility, and ability to form a broad array of derivatives ranging from neurons and glia, to cartilage, bone, and melanocytes. As a uniquely vertebrate cell population, it also offers important clues regarding vertebrate origins. In the past 30 yr, introduction of recombinant DNA technology has facilitated the dissection of the genetic program controlling neural crest development and has provided important insights into gene regulatory mechanisms underlying cell migration and differentiation. More recently, new genomic approaches have provided a platform and tools that are changing the depth and breadth of our understanding of neural crest development at a “systems” level. Such advances provide an insightful view of the regulatory landscape of neural crest cells and offer a new perspective on developmental as well as stem cell and cancer biology.

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Bipolar Disorder (BD) is a highly hereditary and severe disorder. Large genome-wide association studies have identified CACNA1C, a calcium channel gene crucial for brain development and neural function, as a major genetic risk factor for BD. The strongest association is with a SNP located in the third intronic region of the gene, however, the underlying molecular mechanisms of the pathogenesis have not been elucidated yet completely so it restrains efficient treatment and worsens the prognosis. In this project, we provide an integrative approach combining patient-derived stem cells, CRISPR-engineered isogenic lines, and advanced 3D brain organoids to understand the characteristics of the neurodevelopmental disease comprehensively.

Bipolar Disorder (BD) is a highly hereditary and severe disorder. Large genome-wide association studies have identified CACNA1C, a calcium channel gene crucial for brain development and neural function, as a major genetic risk factor for BD. The strongest association is with a SNP located in the third intronic region of the gene, however, the underlying molecular mechanisms of the pathogenesis have not been elucidated yet completely so it restrains efficient treatment and worsens the prognosis. In this project, we provide an integrative approach combining patient-derived stem cells, CRISPR-engineered isogenic lines, and advanced 3D brain organoids to understand the characteristics of the neurodevelopmental disease comprehensively.

Bipolar Disorder (BD) is a highly hereditary and severe disorder. Large genome-wide association studies have identified CACNA1C, a calcium channel gene crucial for brain development and neural function, as a major genetic risk factor for BD. The strongest association is with a SNP located in the third intronic region of the gene, however, the underlying molecular mechanisms of the pathogenesis have not been elucidated yet completely so it restrains efficient treatment and worsens the prognosis. In this project, we provide an integrative approach combining patient-derived stem cells, CRISPR-engineered isogenic lines, and advanced 3D brain organoids to understand the characteristics of the neurodevelopmental disease comprehensively.

This article is from Biology Open , volume 3 . Abstract We previously found that the small GTPase Ras-dva1 is essential for the telencephalic development in Xenopus laevis because Ras-dva1 controls the Fgf8-mediated induction of FoxG1 expression, a key telencephalic regulator. In this report, we show, however, that Ras-dva1 and FoxG1 are expressed in different groups of cells; whereas Ras-dva1 is expressed in the outer layer of the anterior neural fold, FoxG1 and Fgf8 are activated in the inner layer from which the telencephalon is derived. We resolve this paradox by demonstrating that Ras-dva1 is involved in the transduction of Fgf8 signal received by cells in the outer layer, which in turn send a feedback signal that stimulates FoxG1 expression in the inner layer. We show that this feedback signal is transmitted by secreted Agr proteins, the expression of which is activated in the outer layer by mediation of Ras-dva1 and the homeodomain transcription factor Otx2. In turn, Agrs are essential for maintaining Fgf8 and FoxG1 expression in cells at the anterior neural plate border. Our finding reveals a novel feedback loop mechanism based on the exchange of Fgf8 and Agr signaling between neural and non-neural compartments at the anterior margin of the neural plate and demonstrates a key role of Ras-dva1 in this mechanism.

Original Backprop (Version 1.2) is an MS-DOS package of four stand-alone C-language programs that enable users to develop neural network solutions to a variety of practical problems. Original Backprop generates three-layer, feed-forward (series-coupled) networks which map fixed-length input vectors into fixed length output vectors through an intermediate (hidden) layer of binary threshold units. Version 1.2 can handle up to 200 input vectors at a time, each having up to 128 real-valued components. The first subprogram, TSET, appends a number (up to 16) of classification bits to each input, thus creating a training set of input output pairs. The second subprogram, BACKPROP, creates a trilayer network to do the prescribed mapping and modifies the weights of its connections incrementally until the training set is leaned. The learning algorithm is the 'back-propagating error correction procedures first described by F. Rosenblatt in 1961. The third subprogram, VIEWNET, lets the trained network be examined, tested, and 'pruned' (by the deletion of unnecessary hidden units). The fourth subprogram, DONET, makes a TSR routine by which the finished product of the neural net design-and-training exercise can be consulted under other MS-DOS applications.

KAU Faculty of Medicine 3rd year CNS MODULE Anatomy lecture

in this paper, was used a method which use concepts of intelligence artificial, machine learning, deep learning for Classification of Type of Vessels. With a technique from deep learning called Convolutional Neural Network (CNN) was applied to recognize images to identify the type of ship and to use the same method to identify if the vessel. The CNN projected with determined 5 layers, the first layer containing 32 neurons, the second layer with 64 neurons, the third layer with 128 neurons, the fourth layer with 512 neurons. Activation functions for these specified layers contain the ReLU function. The fifth and last layer is the output layer is the output layer, so the number of neurons is equal to the number of vessel type. In our study six classes were used, which are the vessel types, in this layer the activation function was the Softmax. The CNN generate satisfactory results, where could get results of prediction with all corrects answers to identify the ship.

The purpose of the studies to date have been to A) produce and maintain a colony of heterozygote neurofibromin (Nf(sup +/-) in order to produce timed-pregnant neurofibromin knockout (Nf(sup -/-)) embryos. (B) assess the ability of in vitro and in situ studies in order to quantitate the survival, proliferation, migration and differentiation of neural crest cells derived from wild type (Nf(sup +/+)), Nf(sup +/-) and Nf(sup -/-) embryos. To achieve the aim in A, I have mated Nf(sup +/-) male mice with wild type mice to generate a colony of Nf(sup +/-) mice. This has proven more effective than directly mating male/female Nf(sup +/-) mice because Nf(sup +/-) have a greater tendency to cannibalize their litters versus wild-type females, With regards to B) I have firstly found it necessary to pair breeding mice during the day during a precise time window in order to accurately obtain embryonic day 9 (EB) time pregnant embryos. This is due to the narrow/transient time window of early NCC development in mice. Secondly, preliminary experiments strongly suggest that it is not feasible to the analysis neural crest development derived from individual embryos using a tissue culture paradigm but rather to use a in system whereby the NCC are analyzed directly in the embryo (in situ).

The use of quantitative structure property relationships (QSPRs) is proposed for the calculation of dielectric constants. A data set of 497 compounds with a wide variety of functional groups is assembled. These compounds span the dielectric constant range of 1-40. A total of 65 molecular descriptors is calculated for these compounds. These descriptors include the dipole moment, polarizability, counts of elemental types, an mediator of hydrogen bonding capability, charged partial surface area descriptors, and molecular connectivity descriptors. Subsets of these descriptors are used to build models in an attempt to find the best possible correlation between chemical structure and dielectric constant. A total of 70,000 models is examined. Neural networks using the Broyden-Fletcher-Goldfarb-Shanno (BFGS) training algorithm are employed to build the models. A total of 191 models has test set errors less than 2.0 and training set errors less than 3.0, where the errors are calculated as the mean of the absolute values of the residuals for sets of 97 and 350 compounds, respectively.

During the DARPA ANNT Program contract, new neural network architectures were developed to carry out autonomous real-time preprocessing, segmentation, recognition, timing, and control of both spatial and temporal inputs. These architectures contribute to: (1) preprocessing of visual form and motion signals; (2) preprocessing of acoustic signals; (3) adaptive pattern recognition and categorization in an unsupervised learning context; (4) adaptive pattern recognition and prediction in a supervised learning context; (5) processing of temporal patterns using working memory networks, with applications to 3-D object recognition; (6) adaptive timing for task scheduling; (7) adaptive sensory-motor control using head-centered spatial representations of 3-D target position.

This article is from PLoS ONE , volume 9 . Abstract During mouse neocortical development, the Wnt–β-catenin signaling pathway plays essential roles in various phenomena including neuronal differentiation and proliferation of neural precursor cells (NPCs). Production of the appropriate number of neurons without depletion of the NPC population requires precise regulation of the balance between differentiation and maintenance of NPCs. However, the mechanism that suppresses Wnt signaling to prevent premature neuronal differentiation of NPCs is poorly understood. We now show that the HMG box transcription factor Tcf3 (also known as Tcf7l1) contributes to this mechanism. Tcf3 is highly expressed in undifferentiated NPCs in the mouse neocortex, and its expression is reduced in intermediate neuronal progenitors (INPs) committed to the neuronal fate. We found Tcf3 to be a repressor of Wnt signaling in neocortical NPCs in a reporter gene assay. Tcf3 bound to the promoter of the proneural bHLH gene Neurogenin1 (Neurog1) and repressed its expression. Consistent with this, Tcf3 repressed neuronal differentiation and increased the self-renewal activity of NPCs. We also found that Wnt signal stimulation reduces the level of Tcf3, and increases those of Tcf1 (also known as Tcf7) and Lef1, positive mediators of Wnt signaling, in NPCs. Together, these results suggest that Tcf3 antagonizes Wnt signaling in NPCs, thereby maintaining their undifferentiated state in the neocortex and that Wnt signaling promotes the transition from Tcf3-mediated repression to Tcf1/Lef1-mediated enhancement of Wnt signaling, constituting a positive feedback loop that facilitates neuronal differentiation.

This article is from Frontiers in Genetics , volume 5 . Abstract Alcohol intoxicated cells broadly alter their metabolites – among them methyl and acetic acid can alter the DNA and histone epigenetic codes. Together with the promiscuous effect of alcohol on enzyme activities (including DNA methyltransferases) and the downstream effect on microRNA and transposable elements, alcohol is well placed to affect intrinsic transcriptional programs of developing cells. Considering that the developmental consequences of early alcohol exposure so profoundly affect neural systems, it is not unfounded to reason that alcohol exploits transcriptional regulators to challenge canonical gene expression and in effect, intrinsic developmental pathways to achieve widespread damage in the developing nervous system. To fully evaluate the role of epigenetic regulation in alcohol-related developmental disease, it is important to first gather the targets of epigenetic players in neurodevelopmental models. Here, we attempt to review the cellular and genomic windows of opportunity for alcohol to act on intrinsic neurodevelopmental programs. We also discuss some established targets of fetal alcohol exposure and propose pathways for future study. Overall, this review hopes to illustrate the known epigenetic program and its alterations in normal neural stem cell development and further, aims to depict how alcohol, through neuroepigenetics, may lead to neurodevelopmental deficits observed in fetal alcohol spectrum disorders.

This article is from Frontiers in Genetics , volume 5 . Abstract Alcohol intoxicated cells broadly alter their metabolites – among them methyl and acetic acid can alter the DNA and histone epigenetic codes. Together with the promiscuous effect of alcohol on enzyme activities (including DNA methyltransferases) and the downstream effect on microRNA and transposable elements, alcohol is well placed to affect intrinsic transcriptional programs of developing cells. Considering that the developmental consequences of early alcohol exposure so profoundly affect neural systems, it is not unfounded to reason that alcohol exploits transcriptional regulators to challenge canonical gene expression and in effect, intrinsic developmental pathways to achieve widespread damage in the developing nervous system. To fully evaluate the role of epigenetic regulation in alcohol-related developmental disease, it is important to first gather the targets of epigenetic players in neurodevelopmental models. Here, we attempt to review the cellular and genomic windows of opportunity for alcohol to act on intrinsic neurodevelopmental programs. We also discuss some established targets of fetal alcohol exposure and propose pathways for future study. Overall, this review hopes to illustrate the known epigenetic program and its alterations in normal neural stem cell development and further, aims to depict how alcohol, through neuroepigenetics, may lead to neurodevelopmental deficits observed in fetal alcohol spectrum disorders.

The proposed article described the basics of developing an artificial neural network as one of the components of a hybrid expert system for antifault control. The functioning of neurons, their reaction under various operating conditions are considered. A multilayer recurrent artificial neural network is also represented, using the method of back propagation of the error, in general form, and its training is shown. In addition, the application of such a network for analyzing and predicting the state of health of a complex technical system is described.

No abstract available

A significant anomaly, Fuel Valve Pilot Seal Extrusion, is affecting the Shuttle Primary Reaction Control System (PRCS) Thrusters, and has caused 79 to fail. To help address this problem, a Shuttle PRCS Thruster Process Evaluation Team (TPET) was formed. The White Sands Test Facility (WSTF) and Boeing members of the TPET have identified many discrete valve current trace characteristics that are predictive of the problem. However, these are difficult and time consuming to identify and trend by manual analysis. Based on this exhaustive analysis over months, 22 thrusters previously delivered by the Depot were identified as high risk for flight failures. Although these had only recently been installed, they had to be removed from Shuttles OV103 and OV104 for reprocessing, by directive of the Shuttle Project Office. The resulting impact of the thruster removal, replacement, and valve replacement was significant (months of work and hundreds of thousands of dollars). Much of this could have been saved had the proposed Neural Network (NN) tool described in this paper been in place. In addition to the significant benefits to the Shuttle indicated above, the development and implementation of this type of testing will be the genesis for potential Quality improvements across many areas of WSTF test data analysis and will be shared with other NASA centers. Future tests can be designed to incorporate engineering experience via Artificial Neural Nets (ANN) into depot level acceptance of hardware. Additionally, results were shared with a NASA Engineering and Safety Center (NESC) Super Problem Response Team (SPRT). There was extensive interest voiced among many different personnel from several centers. There are potential spin-offs of this effort that can be directly applied to other data acquisition systems as well as vehicle health management for current and future flight vehicles.

Study plan for "Explaining the link between dyslexia susceptibility genes DYX1C1, DCDC2, and KIAA0319 and neural development in healthy adolescents – a DTI – fMRI study". The study is part of the Cognitive development in adolescence: Towards neurogenetic markers and naturalistic experimental design -project.

Study plan for "Explaining the link between dyslexia susceptibility genes DYX1C1, DCDC2, and KIAA0319 and neural development in healthy adolescents – a DTI – fMRI study". The study is part of the Cognitive development in adolescence: Towards neurogenetic markers and naturalistic experimental design -project.

This paper presents the development of a Regional Neural Network for Water Level (RNN-WL) predictions, with an application to the coastal inlets along the South Shore of Long Island, New York. Long-term water level data at coastal inlets are important for studying coastal hydrodynamics sediment transport. However, it is quite common that long-term water level observations may be not available, due to the high cost of field data monitoring. Fortunately, the US National Oceanographic and Atmospheric Administration (NOAA) has a national network of water level monitoring stations distributed in regional scale that has been operating for several decades. Therefore, it is valuable and cost effective for a coastal engineering study to establish the relationship between water levels at a local station and a NOAA station in the region. Due to the changes of phase and amplitude of water levels over the regional coastal line, it is often difficult to obtain good linear regression relationship between water levels from two different stations. Using neural network offers an effective approach to correlate the nonlinear input and output of water levels by recognizing the historic patterns between them. In this study, the RNN-WL model was developed to enable coastal engineers to predict long-term water levels in a coastal inlet, based on the input of data in a remote NOAA station in the region. The RNN-WL model was developed using a feed-forwards, back-propagation neural network structure with an optimized training algorithm. The RNN-WL model can be trained and verified using two independent data sets of hourly water levels. The RNN-WL model was tested in an application to Long Island South Shore. Located about 60-100 km away from the inlets there are two permanent long-term water level stations, which have been operated by NOAA since the 1940s.

This grant proposal set out to determine if neurofibromin plays an important role during early neural crest cell development The objectives of this study were: A) set-up and maintain a viable colony of Nf +/- mice to generate Nf +/+, Nf +/- and Nf -/- embryos. B) Set up a breeding protocol that provides accurately timed pregnant E9 embryos. C) Devise assays to reproducibly assay neural crest cell proliferation and cell death. D) Fix, freeze and collect enough E9 Nf +/+, Nf +/- and Nf -/- embryos with which to generate the relevant data. E) Serially section the embryos in D and perform the proliferation and cell death assays in C to determine whether or not neurofibromin modulates neural crest cell proliferation and cell death in these embryos. To date objectives A-D have been accomplished. Objective E is ongoing and should be completed over the next 6-9 months.

The purpose of our research proposal is to determine how the deletion of Tsc1 and mTOR dysregulation affects thalamus development and function. An addition goal of our research was to use our conditional gene deletion system to test the ability of the mTOR inhibitor rapamycin to ameliorate neurological phenotypes depending upon the time and duration of treatment. During this research period, we further advanced our novel genetic approach to control Tsc1 gene deletion concomitant with cell lineage tracing and biochemical analysis to better understand the developmental aspects of Tuberous Sclerosis. A major set of findings is that we identified cellular, molecular, circuitry, and behavioral changes that occur during development and are specific to distinct temporal roles of Tsc1 and the mTOR pathway. Specifically, we showed that early embryonic deletion of Tsc1 resulted in mTOR dysregulation within 48 hours and this dysregulation persisted throughout the life of the mice; this is the first report of the kinetics of mTOR dysregulation. In addition, we showed that neural circuits that connect the thalamus and cerebral cortex are disrupted by early or late deletion of Tsc1 and that the neural circuit abnormality is first observed at the end of embryogenesis (five days after mTOR dysregulation). Thus, specific phenotypes emerge rapidly and others appear over a more prolonged developmental window. We then used biochemistry to show that proteins involved in synaptic architecture are altered by the early deletion of Tsc1. Finally, we show that behavioral alterations are strongly associated with the time of Tsc1 function. We initiated studies to address our additional and have begun delineate the most effective method and dose of rapamycin that can support development while at the same time effectively suppressing the mTOR pathway.

Progress on the grant, 'Photonic Technology Development for Densely Interconnected Neural Networks', is described. Substantial progress has been made in the following areas. Artificial neural network models (or implementation using photonics have been developed and analyzed. Radial basis function neural networks for analog nonparametric density function estimation and pattern recognition, and multilayer backward error propagation neural networks both for implementation on photonic hardware, have been characterized. Emphasis has been on implementations based on incoherent/coherent double angular multiplexed volume hologram interconnected architectures using photorefractive materials, 2-D source arrays, and optoelectronic spatial light modulators, are emphasized. Our work on optoelectronic smart pixel array spatial light modulators is also summarized. Silicon chips for arrays of neuron unit processing with optical inputs have been fabricated, as have GaAs-based chips incorporating inverted Fabry Perot cavity strained layer multiple quantum well modulators. Experimental results from are given. Results of flip chip bonding using a newly developed Velcro like indium bump bond process are given as well. Also included in this report are personnel supported, lists of publications and presentations, transitions to industry, and patent disclosures.

Neural networks can be thought of as combinations of generic pieces linked together in varying architectures. Many different models and architectures have been presented in the published literature. Networks may differ both in the characterization of their pieces and in the connection patterns of those pieces. In order to exploit the similarities between models, incorporate the differences between models, and automate the process of linking the pieces together, a prototype of a generalized research environment for neural networks is being developed. The main virtue of this generalized environment is the flexibility it provides for testing neural network architectural and processing decisions without having to write programs. The environment encompasses the ability to specify desired characteristics (e.g., activation functions, connection masks, sub-net sizes) as parameters to network creation functions; it does not force a programmer to combine such characteristics by altering the program code itself. This paper initially introduces the generalized research environment, subsequently discusses the architecture of a test case network (the neocognitron), and finally presents the initial results in testing a neocognitron instantiated by the environment.

The Air Force (AF) needs an evolving software tool for guiding decision makers through the complexities of software outsourcing. Previous research identified specific outsourcing strategies and linked them to goals and consequences through a variety of relationship rules. These strategies and relationship rules were inserted into a decision support tool. Since that time, more historical data and outsourcing literature has been collected thus necessitating an update to such a tool. As the number of software outsourcing projects are completed, the AF must capture the outsourcing decision experiences which guided the projects and their outcomes. In order to efficiently incorporate this new experience, the decision tool must be redesigned to allow the additional knowledge to be added in such a way that the decision rule base is automatically updated. With this new feature, the tool would increase its precision of predicting software outsourcing success as the software outsourcing knowledge evolves. Capturing software outsourcing as knowledge instead of raw information will help guide decision makers down paths proven to succeed staying clear of risks that historically plagued software outsourcing projects of the past. Software outsourcing decision makers desire not only a characterization of past experiences and predictions of future outcomes, but also reasons to help them make informed decisions.

One of the key tasks the developing brain must learn is how to navigate within the environment. This skill depends on the brain's ability to establish memories of places and things in the environment so that it can form cognitive maps. Earth's gravity defines the plane of orientation of the spatial environment in which animals navigate, and cognitive maps are based on this plane of orientation. Given that experience during early development plays a key role in the development of other aspects of brain function, experience in a gravitational environment is likely to be essential for the proper organization of brain regions mediating learning and memory of spatial information. Since the hippocampus is the brain region responsible for cognitive mapping abilities, this study evaluated the development of hippocampal structure and function in rats that spent part of their early development in microgravity. Litters of male and female Sprague-Dawley rats were launched into space aboard the Space Shuttle Columbia on either postnatal day eight (P8) or 14 (P14) and remained in space for 16 days. Upon return to Earth, the rats were tested for their ability to remember spatial information and navigate using a variety of tests (the Morris water maze, a modified radial arm maze, and an open field apparatus). These rats were then tested physiologically to determine whether they exhibited normal synaptic plasticity in the hippocampus. In a separate group of rats (flight and controls), the hippocampus was analyzed using anatomical, molecular biological, and biochemical techniques immediately postlanding. There were remarkably few differences between the flight groups and their Earth-bound controls in either the navigation and spatial memory tasks or activity-induced synaptic plasticity. Microscopic and immunocytochemical analyses of the brain also did not reveal differences between flight animals and ground-based controls. These data suggest that, within the developmental window studied, microgravity has minimal long-term impact on cognitive mapping function and cellular substrates important for this function. Any differences due to development in microgravity were transient and returned to normal soon after return to Earth.

The purpose of the research is to (a) develop and test new methods to study the internal visual representation of the shape and surface properties of objects, and the mechanisms that calibrate it, and (b) to use the methods to investigate the representation of contour, shape and surface properties, (c) to use the methods to study the representation of visual space, and (d) visual (re- )calibration mechanisms.

The purpose of the research is to (a) develop and test new methods to study the internal visual representation of the shape and surface properties of objects, and the mechanisms that calibrate it, and (b) to use the methods to investigate the representation of contour, shape and surface properties, (c) to use the methods to study the representation of visual space, and (d) visual (re- )calibration mechanisms.

The purpose of the research is to (a) develop and test new methods to study the internal visual representation of the shape and surface properties of objects, and the mechanisms that calibrate it, and (b) to use the methods to investigate the representation of contour, shape and surface properties, (c) to use the methods to study the representation of visual space, and (d) visual (re- )calibration mechanisms.

The purpose of the research is to (a) develop and test new methods to study the internal visual representation of the shape and surface properties of objects, and the mechanisms that calibrate it, and (b) to use the methods to investigate the representation of contour, shape and surface properties, (c) to use the methods to study the representation of visual space, and (d) visual (re- )calibration mechanisms.

The purpose of the research is to (a) develop and test new methods to study the internal visual representation of the shape and surface properties of objects, and the mechanisms that calibrate it, and (b) to use the methods to investigate the representation of contour, shape and surface properties, (c) to use the methods to study the representation of visual space, and (d) visual (re- )calibration mechanisms.

The purpose of the research is to (a) develop and test new methods to study the internal visual representation of the shape and surface properties of objects, and the mechanisms that calibrate it, and (b) to use the methods to investigate the representation of contour, shape and surface properties, (c) to use the methods to study the representation of visual space, and (d) visual (re- )calibration mechanisms.

Supporting Materials for Impact of Shared Genes and Family Environment in Theory of Mind Development (MSc Project)

LibriVox volunteers bring you 11 recordings of <em>To a Fish</em> by (James) Leigh Hunt. This was the weekly poetry project for the week of October 19th, 2008.

LibriVox volunteers bring you 8 recordings of <em>A Fish Answers</em> by James Leigh Hunt. This was the weekly poetry project for the week of October 26th, 2008.

Dark times for British Catholics hung over England in the days of King Henry VIII. Henry, influenced by the hated Thomas Cromwell, fell into opposition with them, suppressing them, and closing religious houses. In that period a famous shrine, erected centuries earlier at Walsingham and dedicated to our Lady, drew people from far and near for it was a favorite place of pilgrimage and the site of many miracles.<br><br>On their grandmother's and uncle's farm, far removed from this scene of persecution, were Jemmy Reynolds and his sister Joan. For a long time they had been promised the chance to make the pilgrimage to Walsingham, and now at last they were going. Their biggest problem was to find a suitable offering to our Lady, and Joan came upon the idea of presenting a great, fine candle. And so they set out upon a thrilling journey which eventually brings Jem face to face with the crafty Cromwell and King Henry himself.<br><br>What happens when they meet a cunning stranger on the way to the shrine and later when Jem attempts to rescue a friend from Cromwell's power are some of the exciting developments that make A Candle For Our Lady interesting and fast moving. True history and authentic background are woven into this story which provides a taste of the struggles English Catholics knew in a time when cruelty and greed ruled the land. (Summary from original jacket.)

A long poem telling the tragic story of Francesca da Rimini, the duped and adulterous bride, inspired by the character in Dante's Inferno. Published in 1816 and dedicated to Lord Byron, it is considered the pinnacle of Hunt's poetic achievements. Hunt, though having fine artistic sensibilities, was not placed among the first rank of lyric poets, many of whom he championed however. The Story of Rimini was written in prison, where he spent two years for slander of the Prince Regent, and is dramatically and vividly told, with much evocative scene-setting and careful portrayal of emotional conflicts. (Peter Tucker)

Isobel Violet Hunt was a British author renowned for her literary salons, which hosted such notables as H.G. Wells, D.H. Laurence, Henry James, W. Somerset Maugham, Oscar Wilde and Ezra Pound. In White Rose of Weary Leaf (often considered her best work), principal character, Amy, voices many of Hunt's New Woman theories of sexual, financial, and intellectual autonomy. Amy manages to successfully navigate through society in her roles as secretary and governess, until her reputation as an "Adventuress" leads to a supreme test. - summary by Lisa Reichert

James Henry Leigh Hunt, best known as Leigh Hunt, was an English critic, essayist, poet, and writer. - Summary by Wikipedia

An amusing but deeply poignant story, “The Last Ditch” describes the wartime experiences of a British aristocratic family who gradually realize that their old feudal perquisites are passing away in the trenches of the Great War and that unprecedented new forces are pushing out the comfortable old ways. Lady Arles is the matriarch determined to resist to her last breath. Her bohemian young daughter Venice is set on a career as a poet and even dallies with a Socialist lover, but in some ways is the family member who seems the most helpless without her old aristocratic privileges. Another daughter Ilsa brings scandal after scandal to the family because of her endless sexual flings, incorrigible almost to the last page. Audley Bar, beloved by at least two of the Ladies Arles, is the ennui-laden aristocratic adventurer, determined despite his middle age to go forth to war and do his bit, especially after one young friend after another dies on the Western Front. Author Violet Hunt pokes ironical, affectionate fun at her old-fashioned cast of characters, but as an ardent feminist and free-thinker finds ways to show her profound sympathies for the rising poor of England, the previously unprivileged who were finding some new freedoms in the passing of the Old Order. Her novel published while the seemingly endless War was still in full force, Hunt deftly sketches a portrait of a very human family, harrowed by loss and adrift in a new world. - Summary by Expatriate

A travel journal of a year the author spent in Germany. With a preface and two additional chapters by her partner, the novelist Ford Madox Ford (here using the surname Hueffer). - Summary by barbara2

Nine twisty-turny tales of tragic human drama, played out in Victorian parlors, death beds and lonely country roads. This collection of Violet Hunt writings has all the requirements for short story entertainment: flirtatious beauties, mismatched love, ''lung symptoms'', and cruel, cruel fate. Sometimes the horror has a ghostly source, but often the horror is rooted in our very human pathology. - Lisa Reichert

10Captain Sword and Captain Pen: A Poem

By Leigh Hunt

This Poem is the result of a sense of duty, which has taken the Author from quieter studies during a great public crisis. He obeyed the impulse with joy, because it took the shape of verse; but with more pain, on some accounts, than he chooses to express. However, he has done what he conceived himself bound to do; and if every zealous lover of his species were to express his feelings in like manner, to the best of his ability, individual opinions, little in themselves, would soon amount to an overwhelming authority, and hasten the day of reason and beneficence. - Summary by Advertisement

11Peaceful Atom

By Bernice Kohn Hunt

In this children's science book from the early 1960s, the concept of atoms and the science behind them is introduced. The book recounts the history of scientific discoveries related to atoms, radioactivity, and nuclear energy. The author promotes the benefits of atomic power plants and nuclear energy while also exploring other positive uses of radioisotopes. The book pointedly does not discuss the history of nuclear weapons and how the scientific discoveries related to atoms led to the ability to create those weapons. - Summary by Elsie Selwyn

Leigh Hunt was an English poet, essayist and editor best remembered as the host of a literary circle which gathered at his home in Hampstead and attracted many well known writers of the day including Lord Byron, Percy Shelley, John Keats, William Hazlitt, Thomas Moore and Charles Lamb. He wrote many letters to various friends including some Epistles in Verse of which those to Byron, Moore, Hazlitt and Lamb are recorded here. He also made translations from Poets of Antiquity (Homer, Theocritus, Anacreon and Catullus) (Summary by Alan Mapstone)